Synthesis, spectral characterization, antimicrobial evaluation and molecular docking studies of new Cu (II), Zn (II) thiosemicarbazone based on sulfonyl isatin

Abstract

Reaction of 5-(morpholinisulfonyl)isatin (1) with thiosemicarbazide derivative appended the corresponding thiosemicarbazone derivative 3 that further coordinated with copper and zinc acetate to afford copper and zinc complexes 4 and 5, respectively. The structure of the ligand and its two complexes Cu (II) and Zn (II) are confirmed using elemental analysis, molar conductance, spectra data (FT-IR, 1H NMR, 13C NMR, mass spectra), and thermogravimetric analysis (TGA). The ligand bounds to metal complex as neutral tridentate (ONS) donor with tetrahedral geometry structure. Additionally, the ligand forms two five-member rings with metals via carbonyl of isatin derivative, the nitrogen of azomethane (C=N), and sulpher of thiosemicarbazone. The antimicrobial activity was evaluated against two Gram-positive, two Gram-negative bacteria, and one fungal strain. Both complexes revealed antimicrobial activity against the tested strains. In addition, the result exhibited that the zinc complex 5 displayed higher activity than copper complex 4, where the zinc complex 5 showed an inhibition zone between (18 ± 0.20 and 23 ± 0.31) mm and activity index ranged between (84 and 100%) compared with Tetracycline. Moreover, the zinc complex 5 exhibited MIC (24.59–98.42 µM) in comparison to Tetracycline (35.14–140.62 µM). Finally, the in silico molecular docking study for thiosemicarbazone derivatives 3, 4, and 5 were carried out inside five active sites as an antibacterial targets. Among them, the ligand and its metal complexes showed the lower binding affinity and suggested that these derivatives 3, 4, and 5 may possibly be DHFR and topoisomerase IV inhibitors.